Malaria elimination and the need for intensive inter-country cooperation. a critical evaluation of regional technical co-operation in Southern Africa.

BACKGROUND: Malaria elimination requires closely co-ordinated action between neighbouring countries. In Southern Africa several countries have reduced malaria to low levels, but the goal of elimination has eluded them thus far. The Southern Africa Development Community (SADC) Malaria Elimination Eight (E8) initiative was established in 2009 between Angola, Botswana, Eswatini, Mozambique, Namibia, South Africa, Zambia, and Zimbabwe to coordinate malaria interventions aiming to eliminate malaria by 2030. Cross-border coordination is important in malaria elimination settings as it strengthens surveillance, joint planning and implementation, knowledge exchange and optimal use of resources. This paper describes how this collaboration is realized in practice, its achievements and challenges, and its significance for malaria elimination prospects. METHODS: The ministers of health of the E8 countries oversee an intergovernmental technical committee supported by specialist working groups consisting of technical personnel from member countries and partner institutions. These technical working groups are responsible for malaria elimination initiatives in key focus areas such as surveillance, vector control, diagnosis, case management, behaviour change and applied research. The technical working groups have initiated and guided several collaborative projects which lay essential groundwork for malaria elimination. RESULTS: The E8 collaboration has yielded achievements in the following key areas. (1) Establishment and evaluation of malaria border health posts to improve malaria services in border areas and reduce malaria among resident and, mobile and migrant populations. (2) The development of a regional malaria microscopy slide bank providing materials for diagnostic training and proficiency testing. (3) A facility for regional external competency assessment and training of malaria microscopy trainers in collaboration with the World Health Organization. (4) Entomology fellowships that improved capacity in entomological surveillance; an indoor residual spraying (IRS) training of trainers' scheme to enhance the quality of this core intervention in the region. (5) Capacity development for regional malaria parasite genomic surveillance. (6) A mechanism for early detection of malaria outbreak through near real time reporting and a quarterly bulletins of malaria incidence in border districts. CONCLUSIONS: The E8 technical working groups system embodies inter-country collaboration of malaria control and elimination activities. It facilitates sustained interaction between countries through a regional approach. The groundwork for elimination has been laid, but the challenge will be to maintain funding for collaboration at this level whilst reducing reliance on international donors and to build capacities necessary to prepare for malaria elimination.

Border malaria: defining the problem to address the challenge of malaria elimination.

Border malaria is frequently cited as an obstacle to malaria elimination and sometimes used as a justification for the failure of elimination. Numerous border or cross-border meetings and elimination initiatives have been convened to address this bottleneck to elimination. In this Perspective, border malaria is defined as malaria transmission, or the potential for transmission, across or along shared land borders between countries where at least one of them has ongoing malaria transmission. Border malaria is distinct from malaria importation, which can occur anywhere and in any country. The authors' analysis shows that the remaining transmission foci of malaria-eliminating countries tend to occur in the vicinity of international land borders that they share with neighbouring endemic countries. The reasons why international land borders often represent the last mile in malaria elimination are complex. The authors argue that the often higher intrinsic transmission potential, the neglect of investment and development, the constant risk of malaria importation due to cross-border movement, the challenges of implementing interventions in complex environments and uncoordinated action in a cross-border shared transmission focus all contribute to the difficulties of malaria elimination in border areas. Border malaria reflects the limitations of the current tools and interventions for malaria elimination and implies the need for social cohesion, basic health services, community economic conditions, and policy dialogue and coordination to achieve the expected impact of malaria interventions. Given the uniqueness of each border and the complex and multifaceted nature of border malaria, a situation analysis to define and characterize the determinants of transmission is essential to inform a problem-solving mindset and develop appropriate strategies to eliminate malaria in these areas.

Livelihood activities, human mobility, and risk of malaria infection in elimination settings: a case-control study.

BACKGROUND: Livelihood activities and human movements participate in the epidemiology of vector-borne diseases and influence malaria risk in elimination settings. In Saudi Arabia, where malaria transmission intensity varies geographically, it is vital to understand the components driving transmission within specific areas. In addition, shared social, behavioural, and occupational characteristics within communities may provoke the risk of malaria infection. This study aims to understand the relationship between human mobility, livelihood activities, and the risk of malaria infection in the border region of Jazan to facilitate further strategic malaria interventions. In addition, the study will complement and reinforce the existing efforts to eliminate malaria on the Saudi and Yemen border by providing a deeper understanding of human movement and livelihood activities. METHODS: An unmatched case-control study was conducted. A total of 261 participants were recruited for the study, including 81 cases of confirmed malaria through rapid diagnostic tests (RDTs) and microscopy and 180 controls in the Baish Governorate in Jazan Provinces, Saudi Arabia. Individuals who received malaria tests were interviewed regarding their livelihood activities and recent movement (travel history). A questionnaire was administered, and the data was captured electronically. STATA software version 16 was used to analyse the data. Bivariate and multivariate analyses were conducted to determine if engaging in agricultural activities such as farming and animal husbandry, recent travel history outside of the home village within the last 30 days and participating in spiritual gatherings were related to malaria infection status. RESULTS: A logistical regression model was used to investigate components associated with malaria infection. After adjusting several confounding factors, individuals who reported travelling away from their home village in the last 30 days OR 11.5 (95% CI 4.43-29.9), and those who attended a seasonal night spiritual gathering OR 3.04 (95% CI 1.10-8.42), involved in animal husbandry OR 2.52 (95% CI 1.10-5.82), and identified as male OR 4.57 (95% CI 1.43-14.7), were more likely to test positive for malaria infection. CONCLUSION: Human movement and livelihood activities, especially at nighttime, should be considered malaria risk factors in malaria elimination settings, mainly when the targeted area is limited to a confined borderland area.

An insight to better understanding cross border malaria in Saudi Arabia.

BACKGROUND: Border malaria is a major obstacle for the malaria elimination in Saudi Arabia. Today, the southern border of Saudi Arabia is a region where malaria cases are resurging, and malaria control is dwindling mainly due to the humanitarian crisis and the conflict in Yemen. This study analyses the current border malaria epidemiology along the southern border of Saudi Arabia from 2015 to 2018. METHODS: All reported cases maintained by the malaria elimination centres in Aledabi and Baish, Jazan Province, Saudi Arabia, from 2015 to 2018 were analysed to examine the epidemiological changes over time. Pearson's Chi-Square test of differences was utilized to assess differences between the characteristics of imported and local causes and between border cases. A logistic regression model was used to predict imported status was related to living along side of the border area. RESULTS: A total of 3210 malaria cases were reported in Baish and Aledabi malaria centres between 2015 and 2018, of which 170 were classified as local cases and 3040 were classified as imported cases. Reported malaria cases were mainly among males, within the imported cases 61.5% (1868/3039) were residents of the border areas. CONCLUSIONS: Given the complexity of cross-border malaria, creating a malaria buffer zone that covers a certain margin from both sides of the border would allow for a joint force, cross-border malaria elimination programme. To initiate a malaria elimination activity and cases reported as belonging to this zone, rather than being pushed from one country to the other, would allow malaria elimination staff to work collaboratively with local borderland residents and other stakeholders to come up with innovative solutions to combat malaria and reach malaria-free borders.

Changing transmission dynamics among migrant, indigenous and mining populations in a malaria hotspot in Northern Brazil: 2016 to 2020.

BACKGROUND: Roraima state is the northernmost state in Brazil and the primary border-crossing point between Brazil and Venezuela. The uncontrolled surge of malaria in Venezuela, coupled with mass migration of Venezuelans to neighbouring countries and the upward trend in informal mining in the state, pose a serious threat to the broader region, especially to migrant, indigenous and mining populations, jeopardizing malaria elimination efforts. This study describes changes in the epidemiological profile of malaria in Roraima state related to time, place and populations at risk from 2016 to 2020. METHODS: De-identified malaria surveillance data were obtained from the Malaria Epidemiological Surveillance System from 2016 to 2020. Pearson's chi-square tested differences between imported and autochthonous cases. Multivariable logistic regression was used to identify risk factors for imported versus autochthonous cases by demographic characteristics. RESULTS: Odds of being an imported case were higher for Plasmodium falciparum cases (AOR = 2.08). However, as the number of cases from Venezuela decreased in 2020 following closure of the border, the proportion of P. falciparum cases increased markedly, from 6.24% in 2019 to 18.50% in 2020. Over the 5-year period, the odds of being an imported case among miners were about nine times higher than the general population (AOR = 8.99). The proportion of total malaria cases that were among indigenous people increased from 33.09% in 2016 to 54.83% in 2020. Indigenous children had a higher burden of malaria with over 40% of cases in children 0 to 9 years old, compared to 8% in non-indigenous children 0 to 9 years old. In some municipalities, place of infection differed from place of notification, with a large proportion of cases in these municipalities reporting in Boa Vista. CONCLUSIONS: Malaria remains a serious threat in Roraima state, especially among high-risk populations, such as miners, migrants, and indigenous people. As malaria cases have increased among indigenous people and miners, and the proportion of P. falciparum cases has increased, elimination efforts require understanding of these risk factors to tailor interventions appropriately. Furthermore, cross-border surveillance systems need to be urgently strengthened at formal and unofficial border points, especially since the border with Venezuela reopened in July 2021.

Implementation of a novel malaria management strategy based on self-testing and self-treatment in remote areas in the Amazon (Malakit): confronting a-priori assumptions with reality.

BACKGROUND: A novel strategy to combat malaria was tested using a methodology adapted to a complex setting in the Amazon region and a hard-to-reach, mobile community. The intervention strategy tested was the distribution, after training, of malaria self-management kits to gold miners who cross the Surinamese and Brazilian borders with French Guiana to work illegally in the remote mining sites in the forest of this French overseas entity. MAIN TEXT: This article aims at presenting all process and implementation outcomes following the Conceptual Framework of Implementation Fidelity i.e. adherence, including content and exposure, and moderators, comprising participant responsiveness, quality of delivery, facilitation strategies, and context. The information sources are the post-intervention survey, data collected longitudinally during the intervention, a qualitative study, data collected during an outreach mission to a remote gold mining site, supervisory visit reports, in-depth feedback from the project implementers, and videos self-recorded by facilitators based on opened ended questions. As expected, being part of or close to the study community was an essential condition to enable deliverers, referred to as "facilitators", to overcome the usual wariness of this gold mining population. Overall, the content of the intervention was in line with what was planned. With an estimated one third of the population reached, exposure was satisfactory considering the challenging context, but improvable by increasing ad hoc off-site distribution according to needs. Participant responsiveness was the main strength of the intervention, but could be enhanced by reducing the duration of the process to get a kit, which could be disincentive in some places. Regarding the quality of delivery, the main issue was the excess of information provided to participants rather than a lack of information, but this was corrected over time. The expected decrease in malaria incidence became a source of reduced interest in the kit. Expanding the scope of facilitators' responsibilities could be a suitable response. Better articulation with existing malaria management services is recommended to ensure sustainability. CONCLUSIONS: These findings supplement the evaluation outcomes for assessing the relevance of the strategy and provide useful information to perpetuate and transfer it in comparable contexts. TRIAL REGISTRATION: ClinicalTrials.gov.  NCT03695770 . 10/02/2018 "Retrospectively registered".

Seven decades towards malaria elimination in Yunnan, China.

BACKGROUND: Yunnan Province was considered the most difficult place in China for malaria elimination because of its complex malaria epidemiology, heterogeneous ecological features, relatively modest economic development, and long, porous border with three malaria endemic countries: Lao People's Democratic Republic, Myanmar, and Viet Nam. METHODS: Academic publications and grey literature relevant to malaria elimination in Yunnan covering the period from 1950 until 2020 inclusive were considered. The following academic indexes were searched: China Science Periodical Database, China National Knowledge Infrastructure Database, and MEDLINE. Grey literature sources were mainly available from the National Institute of Parasitic Diseases (NIPD), the Chinese Center for Diseases Control and Prevention, and the Yunnan Institute of Parasitic Diseases (YIPD). RESULTS: A malaria elimination campaign in the 1950-1960s, based mainly on mass administration of antimalarial drugs and large-scale vector control, reduced morbidity and mortality from malaria and interrupted transmission in some areas, although elimination was not achieved. Similar strategies were used to contain outbreaks and a resurgence of disease during the 1970s, when malaria services were discontinued. From the 1980s, malaria incidence declined, despite the challenges of large numbers of mobile and migrant populations and an unstable primary health care system in rural areas following economic transformation. Launch of the national malaria elimination programme in 2010 led to adoption of the '1-3-7' surveillance and response strategy specifying timely detection of and response for every case, supported by the establishment of a real-time web-based disease surveillance system and a new primary health care system in rural areas. Border malaria was addressed in Yunnan by strengthening the surveillance system down to the lowest level, cross-border collaboration with neighbouring countries and non-governmental organizations, and the involvement of other sectors. CONCLUSIONS: Seven decades of work to eliminate malaria in Yunnan have shown the importance of political commitment, technically sound strategies with high quality implementation, a robust surveillance and response system at all levels, community participation and effective management of border malaria. The experiences and lessons learned from elimination remain important for prevention re-establishment of malaria transmission in the Province.

Cross-border malaria in Northern Brazil.

BACKGROUND: Cross-border malaria is a major barrier to elimination efforts. Along the Venezuela-Brazil-Guyana border, intense human mobility fueled primarily by a humanitarian crisis and illegal gold mining activities has increased the occurrence of cross-border cases in Brazil. Roraima, a Brazilian state situated between Venezuela and Guyana, bears the greatest burden. This study analyses the current cross-border malaria epidemiology in Northern Brazil between the years 2007 and 2018. METHODS: De-identified data on reported malaria cases in Brazil were obtained from the Malaria Epidemiological Surveillance Information System for the years 2007 to 2018. Pearson's Chi-Square test of differences was utilized to assess differences between characteristics of cross-border cases originating from Venezuela and Guyana, and between border and transnational cases. A logistic regression model was used to predict imported status of cases. RESULTS: Cross-border cases from Venezuela and Guyana made up the majority of border and transnational cases since 2012, and Roraima remained the largest receiving state for cross-border cases over this period. There were significant differences in the profiles of border and transnational cases originating from Venezuela and Guyana, including type of movement and nationality of patients. Logistic regression results demonstrated Venezuelan and Guyanese nationals, Brazilian miners, males, and individuals of working age had heightened odds of being an imported case. Furthermore, Venezuelan citizens had heightened odds of seeking care in municipalities adjacent Venezuela, rather than transnational municipalities. CONCLUSIONS: Cross-border malaria contributes to the malaria burden at the Venezuela-Guyana-Brazil border. The identification of distinct profiles of case importation provides evidence on the need to strengthen surveillance at border areas, and to deploy tailored strategies that recognize different mobility routes, such as the movement of refuge-seeking individuals and of Brazilians working in mining.

Setting-up a cross-border action-research project to control malaria in remote areas of the Amazon: describing the birth and milestones of a complex international project (Malakit).

BACKGROUND: In French Guiana, gold miners working illegally represents a major reservoir of malaria. This mobile population, mainly of Brazilian descent, enters the French Guianese forest from neighbouring countries, Suriname and Brazil. A complex and innovative intervention was piloted as a cooperation with the three involved countries involved to control malaria in this specific population. The principle was that health workers called "facilitators" provide the participants with a self-diagnosis and self-treatment kit along with adequate training and material to rapidly manage an episode of malaria symptoms on their own, when they find themselves isolated from health care services. METHODS: This paper describes the design, development, content of the intervention and players' organization of this multi-country project, the opportunities and constraints encountered, and the lessons learnt at this stage. RESULTS: The choice not to implement the usual "Test and Treat" approach within the community is mainly driven by regulatory reasons. The content of medical messages tends to balance the tension between thoroughness, accuracy and efficacy. The wide range of tools developed through a participatory approach was intended to cope with the challenges of the literacy level of the target population. Despite the difficulties encountered due to language, regulation differences and distance between partners, cooperation was fruitful, due to the complementary of stakeholders, their involvement at all important stages and regular face-to-face meetings. DISCUSSION AND CONCLUSION: This experience shows the feasibility of an ambitious project of action-research in a border malaria context, involving several countries and with a mobile and undocumented population. It reveals some factors of success which may be transferable in analogous settings.

Molecular detection of drug resistant malaria in Southern Thailand.

BACKGROUND: Drug resistance within the major malaria parasites Plasmodium vivax and Plasmodium falciparum threatens malaria control and elimination in Southeast Asia. Plasmodium vivax first-line treatment drug is chloroquine together with primaquine, and the first-line treatment for P. falciparum malaria is artemisinin in combination with a partner drug. Plasmodium vivax and P. falciparum parasites resistant to their respective first-line therapies are now found within Southeast Asia. The resistance perimeters may include high transmission regions of Southern Thailand which are underrepresented in surveillance efforts. METHODS: This study investigated blood samples from malaria centres in Southern Thailand. Genetic loci associated with drug resistance were amplified and sequenced. Drug resistance associated genes Pvmdr1, Pvcrt-o, Pvdhfr, and Pvdhps were characterized for 145 cases of P. vivax malaria, as well as the artemisinin resistance-associated Pfkelch13 gene from 91 cases of P. falciparum malaria. RESULTS: Plasmodium vivax samples from Southern Thai provinces showed numerous chloroquine and antifolate resistance-associated mutations, including SNP and Pvcrt-o K10-insertion combinations suggestive of chloroquine resistant P. vivax phenotypes. A high proportion of the C580Y coding mutation (conferring artemisinin resistance) was detected in P. falciparum samples originating from Ranong and Yala (where the mutation was previously unreported). CONCLUSIONS: The results demonstrate a risk of chloroquine and antifolate resistant P. vivax phenotypes in Southern Thailand, and artemisinin resistant P. falciparum observed as far south as the Thai-Malaysian border region. Ongoing surveillance of antimalarial drug resistance markers is called for in Southern Thailand to inform case management.

Imported Plasmodium falciparum and locally transmitted Plasmodium vivax: cross-border malaria transmission scenario in northwestern Thailand.

BACKGROUND: Cross-border malaria transmission is an important problem for national malaria control programmes. The epidemiology of cross-border malaria is further complicated in areas where Plasmodium falciparum and Plasmodium vivax are both endemic. By combining passive case detection data with entomological data, a transmission scenario on the northwestern Thai-Myanmar border where P. falciparum is likely driven by importation was described, whereas P. vivax is also locally transmitted. This study highlights the differences in the level of control required to eliminate P. falciparum and P. vivax from the same region. METHODS: Malaria case data were collected from malaria clinics in Suan Oi village, Tak Province, Thailand between 2011 and 2014. Infections were diagnosed by light microscopy. Demographic data, including migrant status, were correlated with concomitantly collected entomology data from 1330 mosquito trap nights using logistic regression. Malaria infection in the captured mosquitoes was detected by ELISA. RESULTS: Recent migrants were almost four times more likely to be infected with P. falciparum compared with Thai patients (OR 3.84, p < 0.001) and cases were significantly associated with seasonal migration. However, P. falciparum infection was not associated with the Anopheles mosquito capture rates, suggesting predominantly imported infections. In contrast, recent migrants were equally likely to present with P. vivax as mid-term migrants. Both migrant groups were twice as likely to be infected with P. vivax in comparison to the resident Thai population (OR 1.96, p < 0.001 and OR 1.94, p < 0.001, respectively). Plasmodium vivax cases were strongly correlated with age and local capture rates of two major vector species Anopheles minimus and Anopheles maculatus (OR 1.23, p = 0.020 and OR 1.33, p = 0.046, respectively), suggesting that a high level of local transmission might be causing these infections. CONCLUSIONS: On the Thai-Myanmar border, P. falciparum infections occur mostly in the recent migrant population with a seasonality reflecting that of agricultural activity, rather than that of the local mosquito population. This suggests that P. falciparum was mostly imported. In contrast, P. vivax cases were significantly associated with mosquito capture rates and less with migrant status, indicating local transmission. This highlights the different timelines and requirements for P. falciparum and P. vivax elimination in the same region and underlines the importance of multinational, cross-border malaria control.

Characterization of Plasmodium falciparum genes associated with drug resistance in Hodh Elgharbi, a malaria hotspot near Malian-Mauritanian border.

BACKGROUND: A malaria hotspot in the southeastern region of Mauritania, near the Malian border, may hamper malaria control strategies. The objectives were to estimate the prevalence of genetic polymorphisms associated with drug resistance in Plasmodium falciparum isolates and establish baseline data. METHODS: The study was conducted in two malaria-endemic areas in Hodh Elgharbi, situated in the Malian-Mauritanian border area. Blood samples were collected from symptomatic patients. Single nucleotide polymorphisms in Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps were genotyped using PCR-restriction fragment length polymorphism, DNA sequencing and primer extension. The Pfmdr1 gene copy number was determined by real-time PCR. RESULTS: Of 280 P. falciparum-infected patients, 193 (68.9%) carried the Pfcrt 76T mutant allele. The Pfmdr1 86Y and 184F mutations were found in 61 (23.1%) of 264 isolates and 167 (67.6%) of 247 samples that were successfully genotyped, respectively. Pfmdr1 mutant alleles 1034C, 1042D and 1246Y were rarely observed. Of 102 P. falciparum isolates analysed, ten (9.8%) had more than one copy of Pfmdr1 gene. The prevalence of isolates harbouring at least triple mutant Pfdhfr 51I, 59R, 108 N/T was 42% (112/268), of which 42 (37.5%) had an additional Pfdhps 437G mutation. The Pfdhps 540E mutation was observed in four isolates (1.5%), including three associated with Pfdhfr triple mutant. Only two quintuple mutants (Pfdhfr-51I-59R-108N Pfdhps-437G-540E) were observed. CONCLUSIONS: The observed mutations in Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt may jeopardize the future of seasonal malaria chemoprevention based on amodiaquine-sulfadoxine-pyrimethamine, intermittent preventive treatment for pregnant women using sulfadoxine-pyrimethamine, and treatment with artesunate-amodiaquine. Complementary studies should be carried out to document the distribution, origin and circulation of P. falciparum populations in this region and more widely in the country to assess the risk of the spread of resistance.

Sustaining control: lessons from the Lubombo spatial development initiative in southern Africa.

BACKGROUND: The Lubombo Spatial Development Initiative (LSDI) was a tri-country project between South Africa, Swaziland and Mozambique with the aim of accelerating socio-economic development in the region. The malaria component of the project was introduced to decrease the transmission of malaria in the region. This goal was met but with termination of this project resulted in an upsurge of malaria cases in the sub-region mainly as a result of migration from high transmission areas to low transmission ones. The movement of people across borders in southern Africa remains a challenge in sustaining malaria control and elimination. METHODS: Malaria case data for Swaziland and South Africa were obtained from their respective national Malaria Information Systems. Data for Mozambique was obtained from the Mozambican Ministry of Health. Data obtained during the course of the LSDI project was compared to the case data post the termination of the LSDI. RESULTS: The 12-year period of the LSDI showed a substantial decrease in disease burden amongst the three countries involved when compared to the baseline year of 2000. The decrease in malaria cases was 99 % in South Africa and 98 % in Swaziland. Malaria prevalence in Mozambique decreased by 85 % over the same period. However, after the LSDI ended, between 2012 and 2014, there was an upward trend in case data that was counter to the goal of elimination. CONCLUSION: South Africa and Swaziland benefitted from the LSDI and were able to sustain malaria control and progress to the stage of elimination. Mozambique could not sustain the gains made during the LSDI and case numbers increased. Technical and financial resources are key challenges for malaria control and elimination interventions.

Global Cross-Border Malaria Control Collaborative Initiatives: A Scoping Review.

Malaria remains a global disease of public health concern. Malaria control collaborative initiatives are widely being adopted to reduce malaria burden by various countries. This review sought to describe current and past cross-border malaria control initiatives focusing on key activities, outcomes and challenges. An exhaustive search was conducted in Web of Science, PubMed, Google Scholar and EBSCOhost using the following key words: cross-border malaria control, cross-border malaria elimination, bi-national malaria control and multinational malaria control, in combination with Boolean operators "AND" and "OR". Eleven studies satisfied the inclusion criteria for this review. The majority of collaborative initiatives have been formed within regional developmental and continental bodies with support from political leadership. The studies revealed that joint vector control, cases management, epidemiological data sharing along border regions as well as resource sharing and capacity building are some of the key collaborative initiatives being implemented globally. Collaborative initiatives have led to significant reduction in malaria burden and mortality. The majority of collaborative initiatives are underfunded and rely on donor support. We concluded that cross-border malaria collaborative initiatives have the capacity to reduce malaria burden and mortality along border regions; however, inadequate internal funding and over-reliance on donor funding remain the biggest threats to the survival of collaborative initiatives.

[Challenges of maintaining malaria elimination in China: Cross-border malaria].

China was certificated malaria-free by WHO in 2021 and has continued to maintain malaria elimination. However, there are still huge challenges in malaria control in the border regions between Yunnan Province, China and Myanmar due to lack of geographic barriers and frequent cross-border travel. Hereby, we review the direction contributions of the Global Fund Malaria Program implemented by Health Poverty Action (HPA), an international non-governmental organization (NGO), to malaria elimination in China, and analyze the challenges of malaria control caused by external environmental factors, such as COVID-19, in regions where the Global Fund Malaria Program is implemented. In addition, some suggestions are proposed for cross-border collaboration on malaria control.

Defeating malaria in the North-East region: the forerunner for malaria elimination in India.

India is a malaria endemic country which is targeting malaria elimination by 2027. Transmission intensities are low-to-moderate depending on the region supported by multiple disease vectors. Among these, comparatively North-East India contributes to high proportions of malaria cases annually, the majority of which are due to Plasmodium falciparum (90%). Anopheles minimus and An. baimaii (sibling species in the An. dirus complex) are widely prevalent and incriminated as vectors of malaria. Number of intervention tools were field-evaluated beginning 1988 to date against disease vectors and causative parasites to contain the spread of malaria. These included (i) insecticide-treated netting materials (ITNs) for vector control, (ii) rapid diagnostic tests (RDTs) for in situ diagnosis, and (iii) therapeutic efficacy of artemisinin-based combination therapies (ACTs) for improved drug-policy; all of which were incorporated in healthcare services resulting in substantial disease transmission reduction. Populations of both An. minimus and An. baimaii were observed depleting, instead An. culicifacies s.l. recorded to be fast invading degraded forests and assessed to be resistant to multiple insecticides. Of the two prevalent Plasmodium species, while P. vivax continued to be susceptible to chloroquine therapy, P. falciparum had emerged resistant to most available antimalarial drugs except ACTs over space and time and spreading to peninsular India threatening elimination efforts. Disease transmission trends were observed to be declining for which the state of Assam has made huge strides reporting steady fall in cases each passing year vis-à-vis Meghalaya, Mizoram and Tripura (all sharing international border with Bangladesh), in which malaria transmission remained uninterrupted. Consequently, control of malaria in the North-East region of India is of immediate importance and needs prioritization for intensified disease surveillance and control interventions coupled with improved access to healthcare services mitigating risk of disease outbreaks and spread of drug-resistant malaria helping realize the goal of malaria elimination in the country.

Malaria epidemiology in Kobeni department, southeastern Mauritania from 2015 to 2017.

BACKGROUND: Plasmodium falciparum malaria is endemic in the southern sahelian zone of Mauritania where intense internal and trans-border human and livestock movement occurs. The risk of importation and spread of drug-resistant parasites need to be regularly assessed in this region. The objective of the study was to assess the recent malaria situation near the Mauritania-Mali border. METHODS: Between February 2015 and December 2017, patients with fever or history of fever during the previous 48 h, presenting at the health centre of Kobeni city, were screened for malaria using a rapid diagnostic test (RDT) and microscopic examination of blood smears. The diagnosis was later confirmed by PCR. Cohen's kappa statistics was used to estimate the degree of agreement between diagnostic methods. Fisher's exact test was used to compare proportions. The odds ratio was calculated to measure the association between the use of bed nets and malaria infection. RESULTS: A total of 2326 febrile patients (mean age, 20.2 years) were screened for malaria. The presence of malaria parasites was detected by RDT and microscopy in 53.0% and 49.3% of febrile patients, respectively, and was confirmed by PCR in 59.7% (45 missing data). Of 1361 PCR-positive samples, 1205 (88.5%) were P. falciparum, 47 (3.5%) P. vivax, and 99 (7.3%) P. falciparum-P. vivax mixed infection. Malaria transmission occurred mostly during and shortly after the rainy season. The annual rainfall was relatively low in 2016 (267 mm) and 2017 (274 mm), compared to 2015 (448 mm), and coincided with a decline in malaria prevalence in 2016-2017. Although 71.8% of febrile patients reported to possess at least one bed net in the household in our questionnaire, its reported use was not protective against malaria infection (odds ratio: 1.1, 95% CI: 0.91-1.32). CONCLUSIONS: Our study confirmed that P. falciparum is the dominant species in the sahelian zone and that malaria transmission is seasonal and associated with rainfall in this zone. The application of the current national policy based on rapid and reliable malaria diagnosis, case management with artemisinin-based combination therapy, intermittent preventive treatment for pregnant women, distribution and use of long-lasting insecticide impregnated bed nets, and the planned introduction of seasonal malaria chemoprevention for all children under 6 years old is expected to sustainably reduce malaria transmission in this zone.

Contributing to Elimination of Cross-Border Malaria Through a Standardized Solution for Case Surveillance, Data Sharing, and Data Interpretation: Development of a Cross-Border Monitoring System.

BACKGROUND: Cross-border malaria is a significant obstacle to achieving malaria control and elimination worldwide. OBJECTIVE: This study aimed to build a cross-border surveillance system that can make comparable and qualified data available to all parties involved in malaria control between French Guiana and Brazil. METHODS: Data reconciliation rules based on expert knowledge were defined and applied to the heterogeneous data provided by the existing malaria surveillance systems of both countries. Visualization dashboards were designed to facilitate progressive data exploration, analysis, and interpretation. Dedicated advanced open source and robust software solutions were chosen to facilitate solution sharing and reuse. RESULTS: A database gathering the harmonized data on cross-border malaria epidemiology is updated monthly with new individual malaria cases from both countries. Online dashboards permit a progressive and user-friendly visualization of raw data and epidemiological indicators, in the form of time series, maps, and data quality indexes. The monitoring system was shown to be able to identify changes in time series that are related to control actions, as well as differentiated changes according to space and to population subgroups. CONCLUSIONS: This cross-border monitoring tool could help produce new scientific evidence on cross-border malaria dynamics, implementing cross-border cooperation for malaria control and elimination, and can be quickly adapted to other cross-border contexts.

Human infection with Plasmodium knowlesi on the Laos-Vietnam border.

BACKGROUND: Border malaria in the Greater Mekong region of Southeast Asia poses a serious threat to the health of the ethnic minority populations of the region. Traditionally thought to be caused primarily by the malaria parasites Plasmodium falciparum and Plasmodium vivax, recently a zoonotic parasite, Plasmodium knowlesi, has been identified in some countries of the region. The presence of this parasite poses a challenge to malaria control programmes, as it is maintained in a zoonotic reservoir of forest-dwelling macaque monkeys. METHODS: A cross-sectional malaria parasite species prevalence survey was conducted along the Laos-Vietnam border in the central part of the two countries. Human blood samples were collected from Savannakhet in Laos and Quang Tri in Vietnam between August and October 2010 and assayed for the presence of human malaria parasite species and P. knowlesi. A PCR targeting the 18S small subunit ribosomal RNA gene and circumsporozoite protein gene was used for Plasmodium species identification. RESULTS: Nine cases of P. knowlesi were detected by PCR in blood samples from the Laos side and three from the Vietnam side. All P. knowlesi infections were found in co-infection with P. vivax, with some triple infections of P. knowlesi, P. vivax and P. falciparum detected in Laos. Phylogenetic analysis of these parasites suggests that P. knowlesi is circulating in the Laos-Vietnam border region. CONCLUSION: This report shows that P. knowlesi is transmited on both sides of the Vietnam-Laos border. Continued monitoring of the range and prevalence of P. knowlesi on both the sides of Laos-Vietnam border is of importance to the National Malaria Control Programmes of both countries.

Malaria control along China-Myanmar Border during 2007-2013: an integrated impact evaluation.

BACKGROUND: Implementing effective interventions remain a lot of difficulties along all border regions. The emergence of artemisinin resistance of Plasmodium falciparum strains in the Greater Mekong Subregion is a matter of great concern. China has effectively controlled cross-border transmission of malaria and artemisinin resistance of P. falciparum along the China-Myanmar border. METHODS: A combined quantitative and qualitative study was used to collect data, and then an integrated impact evaluation was conducted to malaria control along the China-Myanmar border during 2007-2013. RESULTS: The parasite prevalence rate (PPR) in the five special regions of Myanmar was decreased from 13.6 % in March 2008 to 1.5 % in November 2013. Compared with the baseline (PPR in March 2008), the risk ratio was only 0.11 [95 % confidence interval (CI), 0.09-0. 14) in November 2013, which is equal to an 89 % reduction in the malaria burden. Annual parasite incidence (API) across 19 Chinese border counties was reduced from 19.6 per 10 000 person-years in 2006 to 0.9 per 10 000 person-years in 2013. Compared with the baseline (API in 2006), the API rate ratio was only 0.05(95 % CI, 0.04-0.05) in 2013, which equates to a reduction of the malaria burden by 95.0 %. Meanwhile, the health service system was strengthened and health inequity of marginalized populations reduced along the international border. CONCLUSION: The effective collaboration between China, Myanmar and the international non-governmental organization promptly carried out the core interventions through simplified processes. The integrated approaches dramatically decreased malaria burden of Chinese-Myanmar border.